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Adenosine A 2A receptor‐mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor‐mediated effects in the rat vas deferens

2003; Wiley; Volume: 85; Issue: 3 Linguagem: Inglês

10.1046/j.1471-4159.2003.01715.x

1471-4159

Glória Queiroz, Carlos Talaia, Jorge Gonçalves,

Receptor Mechanisms and Signaling

Abstract In the epididymal portion of rat vas deferens, facilitation of noradrenaline release mediated by adenosine A 2A receptors, but not that mediated by β 2 ‐adrenoceptors or by direct activation of adenylyl cyclase, was attenuated by blockade of α 2 ‐adrenoceptors and abolished by simultaneous blockade of α 2 ‐adrenoceptors, adenosine A 1 and P2Y receptors. The adenosine A 2A receptor‐mediated facilitation was not changed by inhibitors of protein kinase A, protein kinase G or calmodulin kinase II but was prevented by inhibition of protein kinase C with chelerythrine or bisindolylmaleimide XI. Activation of protein kinase C with phorbol 12‐myristate 13‐acetate caused a facilitation of noradrenaline release that was abolished by bisindolylmaleimide XI and reduced by antagonists of α 2 ‐adrenoceptors, adenosine A 1 and P2Y receptors. Activation of adenosine A 2A receptors attenuated the inhibition of noradrenaline release mediated by the presynaptic inhibitory receptors. This effect was mimicked by phorbol 12‐myristate 13‐acetate and prevented by bisindolylmaleimide XI. It is concluded that adenosine A 2A receptors facilitate noradrenaline release by a mechanism that involves a protein kinase C‐mediated attenuation of effects mediated by presynaptic inhibitory receptors, namely α 2 ‐adrenoceptors, adenosine A 1 and P2Y receptors.